Activation of members of the mitogen-activated protein kinase (MAPK) family represents one of the major mechanisms used by eukaryotic cells to transduce extracellular signals into cellular response (J. Blenis, Proc. Natl. Acad. Sci. USA 90, 5889 (1993); K. J. Blumer et al., TIBS, 19, 236 (1994); E. Cano et al., TIBS 20, 117 (1995); R. Seger et al., FASEB J. 9, 726 (1995); R. J. Davis, TIBS 19, 470 (1994)). One member of this kinase family, p38, has been implicated in signaling pathways used by biologically important stimuli including products of microbial pathogens, cytokines, UV light and increased extracellular osmolarity. Most recently p38 activation was found to be correlated with apoptosis in neuronal cells following withdrawal of nerve growth. p38 is activated by a subset of the known dual specificity MAPK kinases (MEKs or MKKs); low molecular weight GTP-binding proteins RAC1 and Cdc42 have also been shown to play a role in regulating p38 activation by some stimuli. A complete understanding of how p38 activation regulates cellular responses requires identification of specific substrates for this enzyme.